Avelumab With Laser Interstitial Therapy for Recurrent Glioblastoma

Sponsor

Icahn School of Medicine at Mount Sinai (Other)

Overall Status

Completed

CT.gov ID

NCT03341806

Collaborator

(none)

Enrollment

Location

Arm

Actual Duration (Months)

0.3

Patients Per Site Per Month

Study Details

Study Description

Brief Summary

The purpose of the study is to characterize the safety and tolerability of avelumab in combination with Laser Interstitial Thermal Therapy (LITT) for blood barrier disruption in patients with recurrent glioblastoma.

Condition or Disease	Intervention/Treatment	Phase
Glioblastoma GBM	Drug: Avelumab Combination Product: MRI-guided LITT therapy	Phase 1

Detailed Description

This is an open label, non-randomized Phase I study of intravenous avelumab every 2 weeks to be administered after real-time MRI-guided LITT therapy for patients with a first recurrence of a glioblastoma.

The primary objective of the study is to characterize the tolerability and safety profile of avelumab in combination with MRI guided LITT administered to patients diagnosed with recurrent GBM.

Part A, the initial cohort of patients will be treated with intravenous avelumab alone. Part B, patients will receive avelumab in combination with MRI-guided LITT to characterize the tolerability and safety of the combined treatment.

Study Design

Study Type:

Interventional

Actual Enrollment :

13 participants

Allocation:

N/A

Intervention Model:

Single Group Assignment

Masking:

None (Open Label)

Primary Purpose:

Treatment

Official Title:

Phase I Study of PD-L1 Inhibition With Avelumab and Laser Interstitial Thermal Therapy in Patients With Recurrent Glioblastoma

Actual Study Start Date :

Jun 13, 2018

Actual Primary Completion Date :

Oct 13, 2021

Actual Study Completion Date :

Oct 13, 2021

Arms and Interventions

Arm	Intervention/Treatment
Experimental: Patients with Recurrent Glioblastoma Part A - Avelumab Part B - Avelumab + MRI-guided LITT therapy	Drug: Avelumab Avelumab will be administered intravenously every 2 weeks at a dose of 10 mg/kg for 2 cycles Combination Product: MRI-guided LITT therapy (Part B) prior to receiving Avelumab 10 mg/kg every 2 weeks + LITT

Arm

Intervention/Treatment

Experimental: Patients with Recurrent Glioblastoma

Part A - Avelumab Part B - Avelumab + MRI-guided LITT therapy

Drug: Avelumab

Avelumab will be administered intravenously every 2 weeks at a dose of 10 mg/kg for 2 cycles

Combination Product: MRI-guided LITT therapy

(Part B) prior to receiving Avelumab 10 mg/kg every 2 weeks + LITT

Outcome Measures

Primary Outcome Measures

Dose Limiting Toxicity level [4 weeks]
Toxicity will be measured by severity of Adverse events with toxicity grading defined by Cancer Therapy Evaluation Program's (CTEP) v4.0 of National Cancer Institute Common Terminology Criteria for Adverse Events (CTCAE) scale.
Objective response rate (ORR) [6 months]
Tumor response to treatment with avelumab in combination with MRI-guided LITT administered to patients with recurrent GBM by estimation of the objective response rate (ORR) -classified according to the RANO Response Criteria (Proportion of Complete Response, Partial Response, Stable Disease and Progressive Disease)

Secondary Outcome Measures

Progression-free survival [6 months]
The % of progression free survival at 6 months
Overall response rate [6 months]
Overall response rate (proportion of partial and complete responses) will be evaluated according to Rano criteria.

Eligibility Criteria

Criteria

Ages Eligible for Study:

18 Years and Older

Sexes Eligible for Study:

All

Accepts Healthy Volunteers:

Inclusion Criteria:

Patients must have histologically proven GBM from the initial resection.
Patients must have a life expectancy > 16 weeks. Patients must have a Karnofsky performance status of ≥ 60 or ECOG 0 - 2
Patient's requirement for dexamethasone should be ≤ 4mg daily or a stable dose at enrollment.
Patients must have adequate bone marrow, hepatic and renal function and hemoglobin and the test musts be performed within 14 days prior to study Day 1.
Highly effective contraception for both male and female subjects if the risk of conception exists.

Exclusion Criteria:

Known history of autoimmune disorder except diabetes mellitus type 1, vitiligo or hypothyroidism only requiring hormone replacement
Patients who have received any other therapeutic investigational agent within 30 days of enrollment with the exception of the personalized MTA vaccine (NCT03223103) that can be continued throughout the study.
Patients who have received any other therapeutic investigational agent within 30 days of enrollment or prior
Prior placement of intracavitary BCNU-impregnated wafers (Gliadel).
Prior treatment with checkpoint inhibitors, CTL-4 antibody or other immunotherapy agents
Presence of any other active malignancy or prior history of malignancy, except for: basal cell carcinoma of the skin, cervical carcinoma in situ, early stage prostate carcinoma not requiring active treatment.
Prior organ transplantation, including allogeneic stem cell transplantation
Significant acute or chronic infections including, among others: HIV, AIDS, HBV
Pregnancy or lactation